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Article ; Online: Consideration of Research Approaches in Systems Neurobiology.

Perreault, Melissa L

Biological psychiatry global open science

2024 Volume 4, Issue 1, Page(s) 107–109

Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ISSN	2667-1743
ISSN (online)	2667-1743
DOI	10.1016/j.bpsgos.2023.10.003
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Article ; Online: Beyond the Binary: Gender Inclusivity in Schizophrenia Research.

Nolan, Caitlin J / Roepke, Troy A / Perreault, Melissa L

Biological psychiatry

2023 Volume 94, Issue 7, Page(s) 543–549

Abstract: Schizophrenia is a severe neuropsychiatric disorder with significant differences in the incidence and symptomology between cisgender men and women. In recent years, considerably more attention has been on the inclusion of sex and gender in schizophrenia ... ...

Abstract	Schizophrenia is a severe neuropsychiatric disorder with significant differences in the incidence and symptomology between cisgender men and women. In recent years, considerably more attention has been on the inclusion of sex and gender in schizophrenia research. However, the majority of this research has failed to consider gender outside of the socially constructed binary of men and women. As a result, little is known about schizophrenia in transgender and gender-nonconforming populations. In this review, we present evidence showing that transgender and gender-nonconforming individuals have elevated risk of developing schizophrenia, and we discuss minority stress theory and other potential factors that may contribute to this risk. The need for inclusion of transgender and gender-nonconforming communities in schizophrenia research is emphasized, alongside a discussion on considerations and challenges associated with this type of research. Finally, we offer specific strategies to make research on schizophrenia, and research on other neuropsychiatric disorders, more inclusive of those populations that do not fall within the socially constructed gender binary. If we are to succeed in the development of more personalized therapeutic approaches for all, a better understanding of the variability of the human brain is needed.
MeSH term(s)	Male ; Humans ; Female ; Schizophrenia ; Gender Identity ; Transgender Persons/psychology
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2023.03.018
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Article ; Online: Sex differences in neuronal oscillatory activity and memory in the methylazoxymethanol acetate model of schizophrenia.

Albeely, Abdalla M / Williams, Olivia O F / Blight, Colin R / Thériault, Rachel-Karson / Perreault, Melissa L

Schizophrenia research

2024 Volume 267, Page(s) 451–461

Abstract: The methylazoxymethanol acetate (MAM) rodent model is used to study aspects of schizophrenia. However, numerous studies that have employed this model have used only males, resulting in a dearth of knowledge on sex differences in brain function and ... ...

Abstract	The methylazoxymethanol acetate (MAM) rodent model is used to study aspects of schizophrenia. However, numerous studies that have employed this model have used only males, resulting in a dearth of knowledge on sex differences in brain function and behaviour. The purpose of this study was to determine whether differences exist between male and female MAM rats in neuronal oscillatory function within and between the prefrontal cortex (PFC), ventral hippocampus (vHIP) and thalamus, behaviour, and in proteins linked to schizophrenia neuropathology. We showed that female MAM animals exhibited region-specific alterations in theta power, elevated low and high gamma power in all regions, and elevated PFC-thalamus high gamma coherence. Male MAM rats had elevated beta and low gamma power in PFC, and elevated vHIP-thalamus coherence. MAM females displayed impaired reversal learning whereas MAM males showed impairments in spatial memory. Glycogen synthase kinase-3 (GSK-3) was altered in the thalamus, with female MAM rats displaying elevated GSK-3α phosphorylation. Male MAM rats showed higher expression and phosphorylation GSK-3α, and higher expression of GSK-β. Sex-specific changes in phosphorylated Tau levels were observed in a region-specific manner. These findings demonstrate there are notable sex differences in behaviour, oscillatory network function, and GSK-3 signaling in MAM rats, thus highlighting the importance of inclusion of both sexes when using this model to study schizophrenia.
Language	English
Publishing date	2024-04-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2024.04.002
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Zs.A 2351: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Understanding and Rebalancing: A Rapid Scoping Review of Cannabis Research Among Indigenous People.

Schaffrick, Miles / Perreault, Melissa L / Jones, A Maxwell P / Illes, Judy

Cannabis and cannabinoid research

2022 Volume 8, Issue 3, Page(s) 426–433

Abstract: Evidence-based perspectives on and patterns of cannabis use are vital to addressing ethical, legal, and regulatory controversies, but have not yet been mapped for Indigenous people. We searched five databases and used a rapid scoping review methodology ... ...

Abstract	Evidence-based perspectives on and patterns of cannabis use are vital to addressing ethical, legal, and regulatory controversies, but have not yet been mapped for Indigenous people. We searched five databases and used a rapid scoping review methodology to analyze empirical studies with a primary focus on cannabis and Indigenous peoples. Studies were examined for year of publication, origin of study and author groups, methods, and thematic foci. We analyzed 68 studies with publication dates between1983 and 2022. Approximately 90% of articles were written by authors in the same geographic location as the study population. Seventy-one percent (71%) of the articles were written by authors of multiple articles. Four articles acknowledged author Indigeneity. None contained author positionality statements. The majority of studies utilized mixed methods that integrated both qualitative and quantitative components. Two major categories of focus that emerged from the analysis are substance use disorders and prevalence rates (
MeSH term(s)	Humans ; Cannabis ; Mental Health ; Indigenous Peoples
Language	English
Publishing date	2022-11-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2022.0251
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Article ; Online: Correction: Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats.

McCallum, Ryan T / Thériault, Rachel-Karson / Manduca, Joshua D / Russell, Isaac S B / Culmer, Angel M / Doost, Janan Shoja / Martino, Tami A / Perreault, Melissa L

Biology of sex differences

2024 Volume 15, Issue 1, Page(s) 31

Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Published Erratum
ZDB-ID	2587352-0
ISSN	2042-6410 ; 2042-6410
ISSN (online)	2042-6410
ISSN	2042-6410
DOI	10.1186/s13293-024-00605-3
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Article ; Online: Glycogen Synthase Kinase-3: A Focal Point for Advancing Pathogenic Inflammation in Depression.

McCallum, Ryan T / Perreault, Melissa L

Cells

2021 Volume 10, Issue 9

Abstract: Increasing evidence indicates that the host immune response has a monumental role in the etiology of major depressive disorder (MDD), motivating the development of the inflammatory hypothesis of depression. Central to the involvement of chronic ... ...

Abstract	Increasing evidence indicates that the host immune response has a monumental role in the etiology of major depressive disorder (MDD), motivating the development of the inflammatory hypothesis of depression. Central to the involvement of chronic inflammation in MDD is a wide range of signaling deficits induced by the excessive secretion of pro-inflammatory cytokines and imbalanced T cell differentiation. Such signaling deficits include the glutamatergic, cholinergic, insulin, and neurotrophin systems, which work in concert to initiate and advance the neuropathology. Fundamental to the communication between such systems is the protein kinase glycogen synthase kinase-3 (GSK-3), a multifaceted protein critically linked to the etiology of MDD and an emerging target to treat pathogenic inflammation. Here, a consolidated overview of the widespread multi-system involvement of GSK-3 in contributing to the neuropathology of MDD will be discussed, with the feed-forward mechanistic links between all major neuronal signaling pathways highlighted.
MeSH term(s)	Animals ; Depression/complications ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Inflammation/enzymology ; Inflammation/etiology ; Inflammation/pathology
Chemical Substances	Glycogen Synthase Kinase 3 (EC 2.7.11.26)
Language	English
Publishing date	2021-09-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092270
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Article ; Online: Cortical dopamine D5 receptors regulate neuronal circuit oscillatory activity and memory in rats.

Albeely, Abdalla M / Nolan, Caitlin J / Rasmussen, Duncan J / Bailey, Craig D C / Perreault, Melissa L

CNS neuroscience & therapeutics

2023 Volume 29, Issue 9, Page(s) 2469–2480

Abstract: Introduction: The dopamine D5 receptor (D5R) shows high expression in cortical regions, yet the role of the receptor in learning and memory remains poorly understood. This study evaluated the impact of prefrontal cortical (PFC) D5R knockdown in rats on ... ...

Abstract	Introduction: The dopamine D5 receptor (D5R) shows high expression in cortical regions, yet the role of the receptor in learning and memory remains poorly understood. This study evaluated the impact of prefrontal cortical (PFC) D5R knockdown in rats on learning and memory and assessed the role of the D5R in the regulation of neuronal oscillatory activity and glycogen synthase kinase-3 (GSK-3β), processes integral to cognitive function. Materials and methods: Using an adeno-associated viral (AAV) vector, male rats were infused with shRNA to the D5R bilaterally into the PFC. Local field potential recordings were taken from freely moving animals and spectral power and coherence were evaluated in, and between, the PFC, orbitofrontal cortex (OFC), hippocampus (HIP), and thalamus. Animals were then assessed in object recognition, object location, and object in place tasks. The activity of PFC GSK-3β, a downstream effector of the D5R, was evaluated. Results: AAV-mediated knockdown of the D5R in the PFC induced learning and memory deficits. These changes were accompanied by elevations in PFC, OFC, and HIP theta spectral power and PFC-OFC coherence, reduced PFC-thalamus gamma coherence, and increased PFC GSK-3β activity. Conclusion: This work demonstrates a role for PFC D5Rs in the regulation of neuronal oscillatory activity and learning and memory. As elevated GSK-3β activity has been implicated in numerous disorders of cognitive dysfunction, this work also highlights the potential of the D5R as a novel therapeutic target via suppression of GSK-3β.
MeSH term(s)	Rats ; Male ; Animals ; Receptors, Dopamine D5/genetics ; Receptors, Dopamine D5/metabolism ; Glycogen Synthase Kinase 3 beta ; Neurons/metabolism ; Hippocampus/metabolism ; Prefrontal Cortex/metabolism ; Receptors, Dopamine D1/genetics
Chemical Substances	Receptors, Dopamine D5 (137750-35-7) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Receptors, Dopamine D1
Language	English
Publishing date	2023-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.14210
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Zs.A 4537: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Sex differences in neuronal systems function and behaviour: beyond a single diagnosis in autism spectrum disorders.

Williams, Olivia O F / Coppolino, Madeleine / Perreault, Melissa L

Translational psychiatry

2021 Volume 11, Issue 1, Page(s) 625

Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is associated with functional brain alterations that underlie the expression of behaviour. Males are diagnosed up to four times more than females, and sex differences have been ... ...

Abstract	Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is associated with functional brain alterations that underlie the expression of behaviour. Males are diagnosed up to four times more than females, and sex differences have been identified in memory, cognitive flexibility, verbal fluency, and social communication. Unfortunately, there exists a lack of information on the sex-dependent mechanisms of ASD, as well as biological markers to distinguish sex-specific symptoms in ASD. This can often result in a standardized diagnosis for individuals across the spectrum, despite significant differences in the various ASD subtypes. Alterations in neuronal connectivity and oscillatory activity, such as is observed in ASD, are highly coupled to behavioural states. Yet, despite the well-identified sexual dimorphisms that exist in ASD, these functional patterns have rarely been analyzed in the context of sex differences or symptomology. This review summarizes alterations in neuronal oscillatory function in ASD, discusses the age, region, symptom and sex-specific differences that are currently observed across the spectrum, and potential targets for regulating neuronal oscillatory activity in ASD. The need to identify sex-specific biomarkers, in order to facilitate specific diagnostic criteria and allow for more targeted therapeutic approaches for ASD will also be discussed.
MeSH term(s)	Autism Spectrum Disorder/diagnosis ; Brain ; Female ; Humans ; Male ; Sex Characteristics
Language	English
Publishing date	2021-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-021-01757-1
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Article ; Online: Sex differences in innate and adaptive neural oscillatory patterns link resilience and susceptibility to chronic stress in rats.

Thériault, Rachel-Karson / Manduca, Joshua D / Perreault, Melissa L

Journal of psychiatry & neuroscience : JPN

2021 Volume 46, Issue 2, Page(s) E258–E270

Abstract: Background: Major depressive disorder is a chronic illness with a higher incidence in women. Dysregulated neural oscillatory activity is an emerging mechanism thought to underlie major depressive disorder, but whether sex differences in these rhythms ... ...

Abstract	Background: Major depressive disorder is a chronic illness with a higher incidence in women. Dysregulated neural oscillatory activity is an emerging mechanism thought to underlie major depressive disorder, but whether sex differences in these rhythms contribute to the development of symptoms is unknown. Methods: We exposed male and female rats to chronic unpredictable stress and characterized them as stress-resilient or stress-susceptible based on behavioural output in the forced swim test and the sucrose preference test. To identify sex-specific neural oscillatory patterns associated with stress response, we recorded local field potentials from the prefrontal cortex, cingulate cortex, nucleus accumbens and dorsal hippocampus throughout stress exposure. Results: At baseline, female stress-resilient rats innately exhibited higher theta coherence in hippocampal connections compared with stress-susceptible female rats. Following stress exposure, additional oscillatory changes manifested: stress-resilient females were characterized by increased dorsal hippocampal theta power and cortical gamma power, and stress-resilient males were characterized by a widespread increase in high gamma coherence. In stress-susceptible animals, we observed a pattern of increased delta and reduced theta power; the changes were restricted to the cingulate cortex and dorsal hippocampus in males but occurred globally in females. Finally, stress exposure was accompanied by the time-dependent recruitment of specific neural pathways, which culminated in system-wide changes that temporally coincided with the onset of depression-like behaviour. Limitations: We could not establish causality between the electrophysiological changes and behaviours with the methodology we employed. Conclusion: Sex-specific neurophysiological patterns can function as early markers for stress vulnerability and the onset of depression-like behaviours in rats.
MeSH term(s)	Animals ; Brain/physiopathology ; Depressive Disorder, Major/physiopathology ; Female ; Hippocampus/physiopathology ; Male ; Neurons ; Rats ; Resilience, Psychological ; Sex Characteristics ; Stress, Psychological/physiopathology
Language	English
Publishing date	2021-03-26
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1077443-9
ISSN	1488-2434 ; 1180-4882
ISSN (online)	1488-2434
ISSN	1180-4882
DOI	10.1503/jpn.200117
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Article ; Online: GSK-3β Disrupts Neuronal Oscillatory Function to Inhibit Learning and Memory in Male Rats.

Albeely, Abdalla M / Williams, Olivia O F / Perreault, Melissa L

Cellular and molecular neurobiology

2021 Volume 42, Issue 5, Page(s) 1341–1353

Abstract: Alterations in glycogen synthase kinase-3β (GSK-3β) activity have been implicated in disorders of cognitive impairment, including Alzheimer's disease and schizophrenia. Cognitive dysfunction is also characterized by the dysregulation of neuronal ... ...

Abstract	Alterations in glycogen synthase kinase-3β (GSK-3β) activity have been implicated in disorders of cognitive impairment, including Alzheimer's disease and schizophrenia. Cognitive dysfunction is also characterized by the dysregulation of neuronal oscillatory activity, macroscopic electrical rhythms in brain that are critical to systems communication. A direct functional relationship between GSK-3β and neuronal oscillations has not been elucidated. Therefore, in the present study, using an adeno-associated viral vector containing a persistently active mutant form of GSK-3β, GSK-3β(S9A), the impact of elevated kinase activity in prefrontal cortex (PFC) or ventral hippocampus (vHIP) of rats on neuronal oscillatory activity was evaluated. GSK-3β(S9A)-induced changes in learning and memory were also assessed and the phosphorylation status of tau protein, a substrate of GSK-3β, examined. It was demonstrated that increasing GSK-3β(S9A) activity in either the PFC or vHIP had similar effects on neuronal oscillatory activity, enhancing theta and/or gamma spectral power in one or both regions. Increasing PFC GSK-3β(S9A) activity additionally suppressed high gamma PFC-vHIP coherence. These changes were accompanied by deficits in recognition memory, spatial learning, and/or reversal learning. Elevated pathogenic tau phosphorylation was also evident in regions where GSK-3β(S9A) activity was upregulated. The neurophysiological and learning and memory deficits induced by GSK-3β(S9A) suggest that aberrant GSK-3β signalling may not only play an early role in cognitive decline in Alzheimer's disease but may also have a more central involvement in disorders of cognitive dysfunction through the regulation of neurophysiological network function.
MeSH term(s)	Alzheimer Disease/metabolism ; Animals ; Glycogen Synthase Kinase 3 beta/metabolism ; Hippocampus/metabolism ; Male ; Maze Learning ; Neurons/metabolism ; Phosphorylation ; Rats ; tau Proteins/metabolism
Chemical Substances	tau Proteins ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, rat (EC 2.7.11.1)
Language	English
Publishing date	2021-01-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-020-01020-z
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