Cerebral embolization impairs memory function and reduces cholinergic marker enzyme activities in various brain regions in rats

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.

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Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder

International Journal of Molecular Sciences ◽

10.3390/ijms21124503 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4503

Author(s):

Sabah Nisar ◽

Ajaz A. Bhat ◽

Sheema Hashem ◽

Najeeb Syed ◽

Santosh K. Yadav ◽

...

Keyword(s):

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Memory Function ◽

Deep Understanding ◽

Brain Regions ◽

Post Traumatic Stress ◽

Brain Areas ◽

Social Burden ◽

Post Traumatic

Post-traumatic stress disorder (PTSD) is a highly disabling condition, increasingly recognized as both a disorder of mental health and social burden, but also as an anxiety disorder characterized by fear, stress, and negative alterations in mood. PTSD is associated with structural, metabolic, and molecular changes in several brain regions and the neural circuitry. Brain areas implicated in the traumatic stress response include the amygdala, hippocampus, and prefrontal cortex, which play an essential role in memory function. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. Conventional methods of studying PTSD have proven to be insufficient for diagnosis, measurement of treatment efficacy, and monitoring disease progression, and currently, there is no diagnostic biomarker available for PTSD. A deep understanding of cutting-edge neuroimaging genetic approaches is necessary for the development of novel therapeutics and biomarkers to better diagnose and treat the disorder. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review article explains the rationale and practical utility of neuroimaging genetics in PTSD and how the resulting information can aid the diagnosis and clinical management of patients with PTSD.

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Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

eLife ◽

10.7554/elife.00362 ◽

2013 ◽

Vol 2 ◽

Cited By ~ 87

Author(s):

Elizabeth D Kirby ◽

Sandra E Muroy ◽

Wayne G Sun ◽

David Covarrubias ◽

Megan J Leong ◽

...

Keyword(s):

Basolateral Amygdala ◽

Acute Stress ◽

Memory Function ◽

Brain Regions ◽

Hippocampal Neurogenesis ◽

Mammalian Brain ◽

Stress Hormone ◽

Adult Rat ◽

Neural Stem Progenitor Cells ◽

Newborn Neurons

Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain.

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Effects of Bromocriptine on Pituitary Organelle Marker Enzyme Activities in Lactating and Postlactating Rats: Selective Activation of Lysosomal Prolactin Proteolytic Activity

Endocrinology ◽

10.1210/endo-115-3-984 ◽

1984 ◽

Vol 115 (3) ◽

pp. 984-989 ◽

Cited By ~ 4

Author(s):

LUIZ DE MARCO ◽

KEITH MASHITER ◽

BYRON CAUGHEY ◽

TIMOTHY J. PETERS

Keyword(s):

Proteolytic Activity ◽

Enzyme Activities ◽

Marker Enzyme ◽

Selective Activation

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Effects of GABAergic drugs on cholecystokinin-like immunoreactivity and its biosynthesis enzyme activities in rat brain regions

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)40709-9 ◽

1998 ◽

Vol 76 ◽

pp. 150

Author(s):

Takeshi Kato ◽

Maki Suzuki ◽

Takeshi Aizawa

Keyword(s):

Rat Brain ◽

Enzyme Activities ◽

Brain Regions ◽

Rat Brain Regions

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Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit

International Journal of Tryptophan Research ◽

10.1177/1178646920936279 ◽

2020 ◽

Vol 13 ◽

pp. 117864692093627

Author(s):

Masatoshi Yamashita

Keyword(s):

Social Life ◽

Potential Role ◽

Memory Function ◽

Dynamic Change ◽

Central Fatigue ◽

Brain Regions ◽

Kynurenine Pathway ◽

Treadmill Running ◽

Brain Functions ◽

Tryptophan Metabolites

Central fatigue leads to reduced ability to perform mental tasks, disrupted social life, and impaired brain functions from childhood to old age. Regarding the neurochemical mechanism, neuroactive tryptophan metabolites are thought to play key roles in central fatigue. Previous studies have supported the “tryptophan-serotonin enhancement hypothesis” in which tryptophan uptake into extensive brain regions enhances serotonin production in the rat model of exercise-induced fatigue. However, serotonin was transiently released after 30 minutes of treadmill running to exhaustion, but this did not reflect the duration of fatigue. In addition, as the vast majority of tryptophan is metabolized along the kynurenine pathway, possible involvement of the tryptophan-kynurenine pathway in the mechanism of central fatigue induction has been pointed out. More recently, our study demonstrated that uptake of tryptophan and kynurenine derived from the peripheral circulation into the brain enhances kynurenic acid production in rat brain in sleep deprivation–induced central fatigue, but without change in serotonin activity. In particular, dynamic change in glial-neuronal interactive processes within the hypothalamus-hippocampal circuit causes central fatigue. Furthermore, increased tryptophan-kynurenine pathway activity in this circuit causes reduced memory function. This indicates a major potential role for the endogenous tryptophan-kynurenine pathway in central fatigue, which supports the “tryptophan-kynurenine enhancement hypothesis.” Here, we review research on the basic neuronal mechanism underlying central fatigue induced by neuroactive tryptophan metabolites. Notably, these basic findings could contribute to our understanding of latent mental problems associated with central fatigue.

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