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Synaptic Remodeling (synaptic + remodeling)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Candidate genes for panic disorder: insight from human and mouse genetic studies

GENES, BRAIN AND BEHAVIOR, Issue 2007
M. Gratacòs
Panic disorder is a major cause of medical attention with substantial social and health service cost. Based on pharmacological studies, research on its etiopathogenesis has been focused on the possible dysfunction of specific neurotransmitter systems. However, recent work has related the genes involved in development, synaptic plasticity and synaptic remodeling to anxiety disorders. This implies that learning processes and changes in perception, interpretation and behavioral responses to environmental stimuli are essential for development of complex anxiety responses secondary to the building of specific brain neural circuits and to adult plasticity. The focus of this review is on progress achieved in identifying genes that confer increased risk for panic disorder through genetic epidemiology and the use of genetically modified mouse models. The integration of human and animal studies targeting behavioral, systems-level, cellular and molecular levels will most probably help identify new molecules with potential impact on the pathogenetic aspects of the disease. [source]

Age-Related Sympathetic Ganglionic Neuropathology: Human Pathology And Animal Models

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2002
RE. Schmidt
Systematic studies of the autonomic nervous system of human subjects and development of well-defined animal models have begun to substantially improve our understanding of the pathogenesis of autonomic dysfunction in aging and may eventually provide strategies for intervention. Neuropathological studies of the sympathetic ganglia of aged human subjects and rodent models have demonstrated that neuroaxonal dystrophy involving intraganglionic terminal axons and synapses is a robust, unequivocal and consistent neuropathological finding in the aged sympathetic nervous system of man and animals. Quantitative studies have demonstrated that markedly swollen argyrophilic dystrophic axon terminals develop in the prevertebral superior mesenteric (SMG) and coeliac, but to a much lesser degree in the superior cervical ganglia (SCG) as a function of age, sex (males more than females) and diabetes. Dystrophic axons were immunoreactive for neuropeptide Y, tyrosine hydroxylase, dopamine-beta-hydroxylase, trkA and p75(NTR), an immunophenotype consistent with their origin from postganglionic sympathetic neurons, and contained large numbers of highly phosphorylated neurofilaments or tubulovesicular elements. The sympathetic ganglia of aged rodents also showed the hallmark changes of neuroaxonal dystrophy as a function of age and location (many more in the SMG than in the SCG). Plasticity-related synaptic remodeling could represent a highly vulnerable target of the aging process. The fidelity of animal models to the neuropathology of aged humans suggests that similar pathogenetic mechanisms may be involved in both and that therapeutic advances in animal studies may have human application. [source]

Protein Kinase C Activators as Synaptogenic and Memory Therapeutics

ARCHIV DER PHARMAZIE, Issue 12 2009
Miao-Kun Sun
Abstract The last decade has witnessed a rapid progress in understanding of the molecular cascades that may underlie memory and memory disorders. Among the critical players, activity of protein kinase C (PKC) isoforms is essential for many types of learning and memory and their dysfunction, and is critical in memory disorders. PKC inhibition and functional deficits lead to an impairment of various types of learning and memory, consistent with the observations that neurotoxic amyloid inhibits PKC activity and that transgenic animal models with PKC, deficit exhibit impaired capacity in cognition. In addition, PKC isozymes play a regulatory role in amyloid production and accumulation. Restoration of the impaired PKC signal pathway pharmacologically results in an enhanced memory capacity and synaptic remodeling / repair and synaptogenesis, and, therefore, represents a potentially important strategy for the treatment of memory disorders, including Alzheimer's dementia. The PKC activators, especially those that are isozyme-specific, are a new class of drug candidates that may be developed as future memory therapeutics. [source]

Panic comorbidity with bipolar disorder: what is the manic,panic connection?

BIPOLAR DISORDERS, Issue 6 2006
Dean F MacKinnon
Context:, Bipolar/panic comorbidity has been observed in clinical, community and familial samples. As both are episodic disorders of affect regulation, the common pathophysiological mechanism is likely to involve deficits in amygdala-mediated, plasticity-dependent emotional conditioning. Evidence:, Neuronal genesis and synaptic remodeling occur in the amygdala; bipolar and panic disorders have both been associated with abnormality in the amygdala and related structures, as well as in molecules that modulate plasticity, such as serotonin, norepinephrine, brain-derived neurotrophic factor (BDNF) and corticotrophin releasing factor (CRF). These biological elements are involved in behavioral conditioning to threat and reward. Model:, Panic attacks resemble the normal acute fear response, but are abnormally dissociated from any relevant threat. Abnormal reward-seeking behavior is central to both manic and depressive syndromes. Appetites can be elevated or depressed; satisfaction of a drive may fail to condition future behavior. These dissociations may be the result of deficits in plasticity-dependent processes of conditioning within different amygdala subregions. Conclusions:, This speculative model may be a useful framework with which to connect molecular, cellular, anatomic and behavioral processes in panic and bipolar disorders. The primary clinical implication is that behavioral treatment may be critical to restore function in some bipolar patients who respond only partially to medications. [source]