Abstract
Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of Ca2+ signals to achieve synaptic plasticity, provide sites for newer synapses, facilitate learning and memory. One of the common and severe complication of neurodegenerative disease is cognitive impairment, which is said to be closely associated with spine pathologies viz., decreased in spine density, spine length, spine volume, spine size etc. Many treatments targeting neurological diseases have shown to improve the spine structure and distribution. However, concise data on the various modulators of dendritic spines are imperative and a need of the hour. Hence, in this review we made an attempt to consolidate the effects of various pharmacological (cholinergic, glutamatergic, GABAergic, serotonergic, adrenergic, and dopaminergic agents) and non-pharmacological modulators (dietary interventions, enriched environment, yoga and meditation) on dendritic spines structure and functions. These data suggest that both the pharmacological and non-pharmacological modulators produced significant improvement in dendritic spine structure and functions and in turn reversing the pathologies underlying neurodegeneration. Intriguingly, the non-pharmacological approaches have shown to improve intellectual performances both in preclinical and clinical platforms, but still more technology-based evidence needs to be studied. Thus, we conclude that a combination of pharmacological and non-pharmacological intervention may restore cognitive performance synergistically via improving dendritic spine number and functions in various neurological disorders.
Highlights
Small, thin, special hair-like protrusions found on the dendritic processes of neurons are known as dendritic spines
Structural changes in spines contribute to the induction of long-term potentiation (LTP) or long-term depression (LTD), which plays a crucial role in synaptic transmissions
Spinogenesis has a functional role in memory formation and retrieval, and is regulated by multiple factors like P21 activated kinases (PAK), calmodulin-dependent protein kinase II (CaMKII), syndecan-2, Ena/VASP, paralemmin-1, TLCN, post synaptic density (PSD), AF6/afadin, Kalirin-7, Rac1, Semaphorin 3F, Tiam1-Rac1-3-LIMK1/2-Cofilin1, and RhoAROCK1/2-Myosin II pathways
Summary
Thin, special hair-like protrusions found on the dendritic processes of neurons are known as dendritic spines. LTP-induced changes in spines such as enlargement of spine head and shortening of the neck are widely evidenced from many experimental studies, explaining close association between the synaptic plasticity and spine morphology [11]. Recent research explains the drawbacks in traditional way of dendritic spine classifications like the spine head area correlated to PSD may not, be applicable for thin and stubby spines. To overcome such drawbacks a newer approach of clusterization of spines has been developed. This approach automatically groups spines into similar structural classes based on selected algorithm without a prior input. Each spine will be represented as set of value of parameters reflecting its morphology from neck and head size to complex geometrical parameters [19]
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