assessment-dendritic-arborization-dentate-gyrus-hippocampal-region

Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity ...

Arkansas State University

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration.

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling.

Mood disorders such as major depressive disorder and bipolar disorder are chronic and recurrent illnesses that cause significant disability and affect approximately 350 million people worldwide. Currently available biogenic amine treatments provide relief for many and yet fail to ameliorate symptoms for others, highlighting the need to diversify the search for new therapeutic strategies. Here we present recent evidence implicating the role of N-methyl-D-aspartate receptor (NMDAR) signaling in the pathophysiology of mood disorders. The possible role of NMDARs in mood disorders has been supported by evidence demonstrating that: (i) both BPD and MDD are characterized by altered levels of central excitatory neurotransmitters; (ii) NMDAR expression, distribution, and function are atypical in patients with mood disorders; (iii) NMDAR modulators show positive therapeutic effects in BPD and MDD patients; and (iv) conventional antidepressants/mood stabilizers can modulate NMDAR function. Taken together, this evidence suggests the NMDAR system holds considerable promise as a therapeutic target for developing next generation drugs that may provide more rapid onset relief of symptoms. Identifying the subcircuits involved in mood and elucidating the role of NMDARs subtypes in specific brain circuits would constitute an important step toward the development of more effective therapies with fewer side effects.

The role of NMDA receptors in the pathophysiology and treatment of mood disorders.

Alzheimer's disease (AD) is a chronic, neurodegenerative disorder that adversely affects neurons in the brain, ultimately resulting in loss of memory and language, behavioural disturbances, and dependence on caregivers. The strongest risk factor for AD is aging, a risk that doubles every five years after the age of 65 years.(1) Increasing population, longevity, and economic prosperity have contributed to concern of a dementia epidemic in the aging population. Currently, 26 million individuals are affected by AD worldwide, a number that is expected to approximate 106 million by the year 2050, provoking serious clinical, social, ethical, and economical problems.(1.)

Article	Year
Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome. Progress in neuro-psychopharmacology & biological psychiatry\| PubMed ID: 24842803	2014
Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Frontiers in cellular neuroscience\| PubMed ID: 24999318	2014
The role of NMDA receptors in the pathophysiology and treatment of mood disorders. Neuroscience and biobehavioral reviews\| PubMed ID: 25218759	2014
The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease. Physical therapy\| PubMed ID: 25573757	2015

Cristy Phillips

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