Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: a hypothesis

Abstract

Background: Regular, "moderate", physical exercise is an established non-pharmacological form of treatment for depressive disorders. Brain lateralization has a significant role in the progress of depression. External stimuli such as various stressors or exercise influence the higher functions of the brain (cognition and affect). These effects often do not follow a linear course. Therefore, nonlinear dynamics seem best suited for modeling many of the phenomena, and putative global pathways in the brain, attributable to such external influences.

Hypothesis: The general hypothesis presented here considers only the nonlinear aspects of the effects produced by "moderate" exercise and "chronic" stressors, but does not preclude the possibility of linear responses. In reality, both linear and nonlinear mechanisms may be involved in the final outcomes. The well-known neurotransmitters serotonin (5-HT), dopamine (D) and norepinephrine (NE) all have various receptor subtypes. The article hypothesizes that 'Stress' increases the activity/concentration of some particular subtypes of receptors (designated nts) for each of the known (and unknown) neurotransmitters in the right anterior (RA) and left posterior (LP) regions (cortical and subcortical) of the brain, and has the converse effects on a different set of receptor subtypes (designated nth). In contrast, 'Exercise' increases nth activity/concentration and/or reduces nts activity/concentration in the LA and RP areas of the brain. These effects may be initiated by the activation of Brain Derived Neurotrophic Factor (BDNF) (among others) in exercise and its suppression in stress.

Conclusion: On the basis of this hypothesis, a better understanding of brain neurodynamics might be achieved by considering the oscillations caused by single neurotransmitters acting on their different receptor subtypes, and the temporal pattern of recruitment of these subtypes. Further, appropriately designed and planned experiments will not only corroborate such theoretical models, but also shed more light on the underlying brain dynamics.

Figure 1

Typical example of complementary action of some neurotransmitter receptor subtypes. Key: DA: Dopamine; NE: Norepinephrine; 5HT: 5-Hydroxytryptamine or Serotonin.

Figure 2

Schematic diagram of stress activity within the brain.

Figure 3

Some putative biochemical aspects of the hypothesis.

Figure 4

Stress induced Lp growth curve with respect to time (in dimensionless form).

Figure 5

Stress induced La growth curve with respect to time (in dimensionless form).

Figure 6

Schematic diagram of stress-induced exercise activity within the brain.

Figure 8

L_a and L_p interactions with concomitant stress and exercise; h = 0.1.

Figure 9

R_a and R_p interactions with concomitant stress and exercise and h = 0.1.

Figure 7

Oscillatory nature of stress (solid) and exercise (dotted).

Figure 10

Oscillatory behavior of receptor subtype distributions in stress and exercise.

Figure 11

Development of chronic stress among rats based on High Plus Maze (HPM) experiment [1, 44].

Figure 12

Reduction of stress due exercise among rats based on High Plus Maze (HPM) experiment [1, 44].

Figure 13

Natural Decline in Exercise effects among rats based on High Plus Maze (HPM) experiment [1, 44].

Figure 14

Increased in 5-HT due stress (15 min. forced swimming) among Wistar rats [48].