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.

Keywords: dendritic spines; diet; enriched environment; modulators; pharmacological modulators; yoga and meditation.

Figure 1

5-HT7R activates downstream small molecule GTPase’s Cdk5 and Cdc42 leading to actin polymerization and spinogenesis [89] (reused as per the Journal of Neurochemistry copyright permission policy) (CdK5: Cyclin Dependent Kinase5,Cdc42: Cell Division Control Protein 42).

Figure 2

Representative Golgi staining images of dopaminergic neurons in substantia nigra and striatum [90] (reused as per the International Journal of molecular Sciences copyright permission policy). (A) Represents decreased dendritic spine density in substantia nigra of high fat diet (HFD) mice compared to control. (B) Represents decreased dendritic spine density in striatum of high fat diet (HFD) mice compared to control. * indicates the significant difference with respect to control.

Figure 3

Pharmacological and non-pharmacological targets on structural pathways in dendritic spine. In the figure, the descriptions in red colour indicates pharmacological modulators and blue indicates non-pharmacological modulators on various phases of dendritic spine morphogenesis. (+) denotes positive modulation; (−) indicates negative modulation. NMDAR: N-methyl-D-aspartate receptor, AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, cdK5: Cyclin dependent kinase-5, BDNF: Brain derived neurotrophic factor, CaMKII: Calcium/calmodulin-dependent protein kinase II, TrKB: Tropomyosin receptor kinase-B, TIAM1: T-cell lymphoma invasion and metastasis-inducing protein 1, cdc42: Cell division control protein 42, WASP: Wiskott-Aldrich syndrome protein.