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Article ; Online: Seasonal fluctuations in BDNF regulate hibernation and torpor in golden-mantled ground squirrels.

Hernandez, Caterina M / Florant, Gregory L / Stranahan, Alexis M

American journal of physiology. Regulatory, integrative and comparative physiology

2024 Volume 326, Issue 4, Page(s) R311–R318

Abstract: Aphagic hibernators such as the golden-mantled ground squirrel (GMGS; ...

Abstract	Aphagic hibernators such as the golden-mantled ground squirrel (GMGS;
MeSH term(s)	Animals ; Hibernation/physiology ; Brain-Derived Neurotrophic Factor/metabolism ; Seasons ; Body Temperature/physiology ; Sciuridae/metabolism
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00186.2023
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Article ; Online: Visceral adiposity, inflammation, and hippocampal function in obesity.

Stranahan, Alexis M

Neuropharmacology

2021 Volume 205, Page(s) 108920

Abstract: The 'apple-shaped' anatomical pattern that accompanies visceral adiposity increases risk for multiple chronic diseases, including conditions that impact the brain, such as diabetes and hypertension. However, distinguishing between the consequences of ... ...

Abstract	The 'apple-shaped' anatomical pattern that accompanies visceral adiposity increases risk for multiple chronic diseases, including conditions that impact the brain, such as diabetes and hypertension. However, distinguishing between the consequences of visceral obesity, as opposed to visceral adiposity-associated metabolic and cardiovascular pathologies, presents certain challenges. This review summarizes current literature on relationships between adipose tissue distribution and cognition in preclinical models and highlights unanswered questions surrounding the potential role of tissue- and cell type-specific insulin resistance in these effects. While gaps in knowledge persist related to insulin insensitivity and cognitive impairment in obesity, several recent studies suggest that cells of the neurovascular unit contribute to hippocampal synaptic dysfunction, and this review interprets those findings in the context of progressive metabolic dysfunction in the CNS. Signalling between cerebrovascular endothelial cells, astrocytes, microglia, and neurons has been linked with memory deficits in visceral obesity, and this article describes the cellular changes in each of these populations with respect to their role in amplification or diminution of peripheral signals. The picture emerging from these studies, while incomplete, implicates pro-inflammatory cytokines, insulin resistance, and hyperglycemia in various stages of obesity-induced hippocampal dysfunction. As in the parable of the five blind wanderers holding different parts of an elephant, considerable work remains in order to assemble a model for the underlying mechanisms linking visceral adiposity with age-related cognitive decline.
MeSH term(s)	Animals ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/immunology ; Cognitive Dysfunction/metabolism ; Hippocampus/immunology ; Hippocampus/metabolism ; Hippocampus/physiopathology ; Humans ; Hyperglycemia/etiology ; Hyperglycemia/immunology ; Hyperglycemia/metabolism ; Hyperinsulinism/etiology ; Hyperinsulinism/immunology ; Hyperinsulinism/metabolism ; Inflammation/etiology ; Inflammation/immunology ; Inflammation/metabolism ; Obesity, Abdominal/complications ; Obesity, Abdominal/immunology ; Obesity, Abdominal/metabolism
Language	English
Publishing date	2021-12-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2021.108920
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Article ; Online: Region-specific targeting of microglia in vivo using direct delivery of tamoxifen metabolites via microfluidic polymer fibers.

Stranahan, Alexis M / Tabet, Anthony / Anikeeva, Polina

Brain, behavior, and immunity

2023 Volume 115, Page(s) 131–142

Abstract: Region-specific genetic manipulation of glial cells remains challenging due to the lack of anatomically selective transgenic models. Although local transduction is achievable with viral vectors, uniform recombination can be challenging in larger brain ... ...

Abstract	Region-specific genetic manipulation of glial cells remains challenging due to the lack of anatomically selective transgenic models. Although local transduction is achievable with viral vectors, uniform recombination can be challenging in larger brain regions. We investigated the efficacy of intraparenchymal delivery of the tamoxifen metabolite endoxifen using inducible cre reporter mice. After observing localized reporter induction following stereotaxic injections of endoxifen in CX3CR1creERT2 mice, we carried out chronic delivery via osmotic pumps attached to bilateral cannulas made of stainless steel or microfluidic polymer fibers. Analysis of reporter expression in sections or iDISCO-cleared brains from TMEM119creERT2 mice revealed widespread induction following chronic infusion. Neuronal damage and gliosis were more prevalent around steel cannulas than polymer fibers, and glial reactivity was further attenuated when devices were implanted two months before drug delivery. In summary, region-specific recombination is achievable in glia with minimal tissue damage after endoxifen delivery via microfluidic polymer implants.
MeSH term(s)	Mice ; Animals ; Microglia/metabolism ; Polymers ; Microfluidics ; Tamoxifen/pharmacology
Chemical Substances	4-hydroxy-N-desmethyltamoxifen (46AF8680RC) ; Polymers ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2023-10-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.09.021
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Zs.A 2276: 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)
Zs.MO 327: Show issues

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Article ; Online: Metabolic regulation of aging and age-related disease.

Hamrick, Mark W / Stranahan, Alexis M

Ageing research reviews

2020 Volume 64, Page(s) 101175

Abstract: Inquiry into relationships between energy metabolism and brain function requires a uniquely interdisciplinary mindset, and implementation of anti-aging lifestyle strategies based on this work also involves consistent mental and physical discipline. Dr. ... ...

Abstract	Inquiry into relationships between energy metabolism and brain function requires a uniquely interdisciplinary mindset, and implementation of anti-aging lifestyle strategies based on this work also involves consistent mental and physical discipline. Dr. Mark P. Mattson embodies both of these qualities, based on the breadth and depth of his work on neurobiological responses to energetic stress, and on his own diligent practice of regular exercise and caloric restriction. Dr. Mattson created a neurotrophic niche in his own laboratory, allowing trainees to grow their skills, form new connections, and eventually migrate, forming their own labs while remaining part of the extended lab family. In this historical review, we highlight Dr. Mattson's many contributions to understanding neurobiological responses to physical exercise and dietary restriction, with an emphasis on the mechanisms that may underlie neuroprotection in ageing and age-related disease. On the occasion of Dr. Mattson's retirement from the National Institute on Aging, we highlight his foundational work on metabolism and neuroplasticity by reviewing the context for these findings and considering their impact on future research on the neuroscience of aging.
MeSH term(s)	Aging ; Caloric Restriction ; Energy Metabolism ; Exercise ; Humans ; Neuronal Plasticity
Language	English
Publishing date	2020-09-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2020.101175
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Zs.A 5579: Show issues

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Article: Changes in Brain Neuroimmunology Following Injury and Disease.

Tabet, Anthony / Apra, Caroline / Stranahan, Alexis M / Anikeeva, Polina

Frontiers in integrative neuroscience

2022 Volume 16, Page(s) 894500

Abstract: The nervous and immune systems are intimately related in the brain and in the periphery, where changes to one affect the other and vice-versa. Immune cells are responsible for sculpting and pruning neuronal synapses, and play key roles in neuro- ... ...

Abstract	The nervous and immune systems are intimately related in the brain and in the periphery, where changes to one affect the other and vice-versa. Immune cells are responsible for sculpting and pruning neuronal synapses, and play key roles in neuro-development and neurological disease pathology. The immune composition of the brain is tightly regulated from the periphery through the blood-brain barrier (BBB), whose maintenance is driven to a significant extent by extracellular matrix (ECM) components. After a brain insult, the BBB can become disrupted and the composition of the ECM can change. These changes, and the resulting immune infiltration, can have detrimental effects on neurophysiology and are the hallmarks of several diseases. In this review, we discuss some processes that may occur after insult, and potential consequences to brain neuroimmunology and disease progression. We then highlight future research directions and opportunities for further tool development to probe the neuro-immune interface.
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452962-X
ISSN	1662-5145
ISSN	1662-5145
DOI	10.3389/fnint.2022.894500
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Article ; Online: Introduction to the special issue of ageing research reviews on synaptic global positioning systems.

Stranahan, Alexis M

Ageing research reviews

2013 Volume 12, Issue 3, Page(s) 737–738

MeSH term(s)	Aging/physiology ; Animals ; Brain/physiology ; Humans ; Signal Transduction ; Synapses/physiology
Language	English
Publishing date	2013-06
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2013.05.005
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Zs.A 5579: Show issues

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Article ; Online: Chronobiological approaches to Alzheimer's disease.

Stranahan, Alexis M

Current Alzheimer research

2012 Volume 9, Issue 1, Page(s) 93–98

Abstract: Dynamic circadian rhythms contribute to memory formation, and the hormonal and neurochemical changes that follow circadian patterns are frequently dysregulated with aging. The effect of aging on circadian rhythms is a double-edged sword; on one hand, ... ...

Abstract	Dynamic circadian rhythms contribute to memory formation, and the hormonal and neurochemical changes that follow circadian patterns are frequently dysregulated with aging. The effect of aging on circadian rhythms is a double-edged sword; on one hand, poor sleep quality compromises neuronal structure and function in regions that support cognition, and on the other hand, perturbation of central and peripheral oscillators changes the hormonal milieu, with consequences for neuroplasticity. In the current review, recent developments surrounding the circadian regulation of memory formation are described, with reference to how mechanisms that support temporal coding might change with advancing age. The cognitive consequences of changes in sleep patterns are also discussed. New roles for the circadian clock genes period-1, period-2, and bmal1 in memory formation are discussed in the context of age-related cognitive decline. The potential for chronobiological approaches to the treatment and prevention of Alzheimer's disease merits further exploration from a pharmacotherapeutic perspective, as the timing of drug delivery could potentiate or diminish treatment efficacy.
MeSH term(s)	Aging/physiology ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Animals ; Chronobiology Phenomena/physiology ; Circadian Rhythm Signaling Peptides and Proteins/genetics ; Circadian Rhythm Signaling Peptides and Proteins/metabolism ; Hippocampus/metabolism ; Humans ; Memory/physiology ; Suprachiasmatic Nucleus/metabolism
Chemical Substances	Circadian Rhythm Signaling Peptides and Proteins
Language	English
Publishing date	2012-01-26
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2205170-3
ISSN	1875-5828 ; 1567-2050
ISSN (online)	1875-5828
ISSN	1567-2050
DOI	10.2174/156720512799015028
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Zs.A 6235: Show issues

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Article ; Online: Beige adipocytes mediate the neuroprotective and anti-inflammatory effects of subcutaneous fat in obese mice.

Guo, De-Huang / Yamamoto, Masaki / Hernandez, Caterina M / Khodadadi, Hesam / Baban, Babak / Stranahan, Alexis M

Nature communications

2021 Volume 12, Issue 1, Page(s) 4623

Abstract: Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking ... ...

Abstract	Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.
MeSH term(s)	Adipocytes, Beige/cytology ; Adipocytes, Beige/metabolism ; Adipose Tissue, Beige/metabolism ; Adiposity ; Animals ; Anti-Inflammatory Agents/metabolism ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/physiopathology ; Diet, High-Fat/adverse effects ; Humans ; Interleukin-4/metabolism ; Mice, Obese ; Neuronal Plasticity/physiology ; Neuroprotective Agents/metabolism ; Obesity/etiology ; Obesity/metabolism ; Obesity/physiopathology ; Subcutaneous Fat/metabolism ; Subcutaneous Fat/transplantation ; T-Lymphocytes/metabolism ; Mice
Chemical Substances	Anti-Inflammatory Agents ; Neuroprotective Agents ; Interleukin-4 (207137-56-2)
Language	English
Publishing date	2021-07-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-24540-8
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Article ; Online: Physiological variability in brain-derived neurotrophic factor expression predicts dendritic spine density in the mouse dentate gyrus.

Stranahan, Alexis M

Neuroscience letters

2011 Volume 495, Issue 1, Page(s) 60–62

Abstract: Dendritic spines are the predominant sites of excitatory neurotransmission in the adult brain, and brain-derived neurotrophic factor (BDNF) is a well-characterized determinant of dendritic spine number and morphology. The relationship between BDNF ... ...

Abstract	Dendritic spines are the predominant sites of excitatory neurotransmission in the adult brain, and brain-derived neurotrophic factor (BDNF) is a well-characterized determinant of dendritic spine number and morphology. The relationship between BDNF expression and dendritic spine number is particularly evident in the hippocampus, where environmental conditions that enhance hippocampal BDNF levels also promote local increases in dendritic spine density. However, the relationship between physiological variability in hippocampal BDNF expression and spine number has yet to be assessed. To determine whether natural variability in BDNF expression is associated with hippocampal dendritic spine number, correlations between BDNF protein levels and dendritic spine density among Golgi-impregnated neurons in the hippocampal dentate gyrus and CA1 subfields were assessed in adult male C57Bl/6J mice. In the dentate gyrus, but not in the apical oblique dendrites of CA1 pyramidal cells, BDNF protein expression was significantly correlated with dendritic spine density. This observation suggests that there may be a subregionally specific relationship between hippocampal BDNF expression and the density of spines.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/biosynthesis ; CA1 Region, Hippocampal/metabolism ; CA1 Region, Hippocampal/ultrastructure ; Dendritic Spines/ultrastructure ; Dentate Gyrus/metabolism ; Dentate Gyrus/ultrastructure ; Male ; Mice
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2011-03-21
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2011.03.037
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Zs.A 1166: Show issues

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Article ; Online: Similarities and differences in spatial learning and object recognition between young male C57Bl/6J mice and Sprague-Dawley rats.

Stranahan, Alexis M

Behavioral neuroscience

2011 Volume 125, Issue 5, Page(s) 791–795

Abstract: Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular ... ...

Abstract	Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular contributes to both spatial learning and recognition memory, but the extent to which rats and mice are comparable in these two cognitive domains remains unclear. To evaluate potential species differences in spatial memory and object recognition, young adult male Sprague-Dawley rats and male C57Bl/6J mice were tested in the water maze and novel object recognition tasks. Following six days of training, with four trials per day, there was no difference in the ability of rats and mice to learn the location of a hidden platform. However, rats performed better than mice on the probe trial, indicative of superior retention. In the novel object preference test, no species differences in recognition memory were detected, although rats spent more time exploring the arena and took longer to approach the objects. These observations suggest that while species differences in spatial memory retention are present, they do not correlate with differences in object recognition memory.
MeSH term(s)	Animals ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley ; Reaction Time/physiology ; Recognition, Psychology/physiology ; Spatial Behavior/physiology ; Species Specificity ; Visual Perception/physiology
Language	English
Publishing date	2011-09-26
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	230159-3
ISSN	1939-0084 ; 0735-7044
ISSN (online)	1939-0084
ISSN	0735-7044
DOI	10.1037/a0025133
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