Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain

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.

Molecular insights into enriched environments and behavioral improvements in autism: a systematic review and meta-analysis

“…In addition to improving synaptic function, the beneficial effects of EE are closely associated with enhanced synaptic structure balance in basal dendritic length and spine density across various regions, including the cortex, hippocampus, striatum, and amygdala ( 7 , 9 , 60 ). On one hand, EE has demonstrated an ability to improve synaptogenesis and complex arbor formation, contributing to enhanced dendritic spines ( 7 , 9 , 61 ). On the other hand, EE significantly reverses decreased dendritic spine density, the number of mushroom spines, and disruptions in synapse remodeling ( 9 , 13 , 62 – 64 ).…”

Post-Synapses in the Brain: Role of Dendritic and Spine Structures

“…The complexity of such signaling does not depend only on the nature of the received pre-synaptic messages. It is also due to the complexity and functionality of the two types of post-synaptic structures, one located at flat or indented areas of dendritic fibers, the other at the spines, small expansions connected to dendritic fibers by their neck [ 8 , 9 ]. Additional types of post-synapses, located not at dendritic fibers but at neuronal bodies [ 1 ], will not be considered in the present review.…”

“…In the brain, the distribution of flat/intended and that of spinal post-synapses are not random. Coverage by flat/intended predominates in dendritic fibers of inhibitory neurons; coverage by spines (discovered by Santiago Ramon y Cajal at the end of the 19th century) accounts for almost all dendritic fibers from excitatory neurons [ 8 ]. Functionally the two types of post-synapses may appear largely analogous.…”

“…However, in specific effects such as plasticity, relevant for processes including differentiation/de-differentiation, learning and memory, the flat-to-spine prominence is considerable [ 9 , 10 , 11 ]. Additional properties, such as structures, molecular composition, mechanisms, dynamics and time-dependence of their activity, are more relevant or specific of the spines [ 3 , 8 , 10 , 11 , 12 ].…”

“…This is because many important properties of these structures had been established in previous decades [ 1 , 2 , 3 , 4 , 5 , 6 ]. Section 2 , dedicated to spine synapses, is longer because knowledge about these structures has grown considerably during the last several years [ 8 , 10 , 11 , 12 ], and recent developments have revealed important news and also a few aspects that at present are known only partially [ 8 , 11 , 13 ]. Finally, a Section 3 has been included dedicated to the role of post-synaptic processes in a few brain diseases, illustrating processes of relevance in which the two forms of post-synapses induce peculiar operational properties.…”