Exercise makes a differance at the cellular level.

The molecular basis of exercise and its impact for maintaining neural function and plasticity has been found, the effect of BDNF (Brain Derieved Neutrophic Factor). BDNF seen to promote neuronal repair, learning and memory. Exercise helps to augment synaptic plasticity, promote behavioural rehabilitation and counteract deletrious effect of aging. Central nervous system has the regeneration potential. The effect of exercise go beyond simply increasing regional blood supply/ motor- sensory regions of the brain. Mailoo VJ (2006) even explored correlation of immune system and mind in Psychoneuroimmunolgical studies for different disease conditions.

Neutrotrophic Factors

Neutrotrophic factors regulates the proliferation and differentiation of cells in the Central Nervous System. The Neutrotrophic factors elevated by exercise are- Insulin like Growth Factor (IGF), Fibroblast Growth Factor2 (FGF2) and BDNF. The release and regulation of BDNF is activity dependent whereas release of other neutrotrophic factors like Nerve Growth Factor (NGF), NT3 and NT4 expressions are not activity dependent.

Brain Derieved Neutrotrophic Factor (BDNF)

BDNF secretions are of two types mainly- Regulated (Once synthesised the Neurotrophins are stored in secreatory granules and are released in response to Extracellular cues) and Constitutive (Released spontaneously after being synthesised. So these are continuously available to cells that needs it).

Exercise and BDNF

Exercise induces the expression of BDNF mRNA and protein in cerebral cortex, Cerebellum and Spinal Cord. This is the non invasive paradigm to activate the plastic potential of injured CNS by employing BDNF and similar trophic support factor. Exercise improves cognitive abilities. Animals who learned fastest and had best recall had highest BDNF levels. BDNF improves learning, memory tasks and long term potentiatiation (LTP). BDNF plays role in consolidating Short Term Memory to Long term memory. Other Neutrotrophic factors like NGF/ NT3 doesnot seen to have similar effect. Most of the BDNF researches are on rats or other animals. Chronic delievary of BDNF in human patients is difficult as it is unable to cross the blood brain barrier and also infusing it in human brain will be too invasive. Hence the importance of exercise in Neurorehabilitation Therapy.

BDNF and Protein regulation

BDNF increases the Transcriptional Regulator cAMP response element binding protein (CREB). CREB activates de NOVO transcription and translation of inducible transcription factors such as cFOS and JUN, which results in more persistent expression of target gene. CREB disruption has resulted in memory impairement in Drosophila and mice. Animals with highest BDNF expression had the highest CREB expression and the best memory recall. BDNF regulates syneptic protein called SYNAPSIN I. Inhibiting Synapsin I reduces both the synaptic vesicle reserve pool and Neurotransmitter release . Blocking the action of BDNF produces synaptic fatigue and decreased SYNAPSIN I levels. In epileptics clinical study found genetic mutation in Synapsin I gene to be associated with learning difficulties. Synapsin I functions by: regulating neurite development, formation and maintenance of pre synaptic structures, axonal elongation and new synaptic formation.

Exercise and brain

Exercise has therapeutic effect on injured brain by:

• Reducing degree of initiatory damage.
• Limiting amount of secondary neuronal death.
• Supporting neural repair.
• Behavioural rehabilitation.

Exercise therapy may be beneficial for people who had sustained TIA and have a high disposition to experience secondary insult. In animal research it is seen that use of exercise immediately following traumatic brain injury can exaggerate the extent of ischaemia/ Traumatic Brain Injury (TBI). It has been seen that post injury cellular ATP availability is low. Exercise increases the energy demand of various brain parts like hippocampus, motor cortex and the striatum, hence the likelihood that physical activity during energetically compromised time may accelerate cellular dysfunction. When exercise is delayed by about 14 days post injury, it enhances BDNF and cognitive function.

BDNF and Synapses

BDNF improves synaptic function and Neurite outgrowth in Spinal Cord and innervated skeletal muscle. BDNF localizes to synaptic vesicles in dorsal horn and modulates sensory input within the spinal cord.

Conclusion
It is seen that repetitive loading of hind limb during running produces increase in BDNF levels. Exercise should be considered as an important tool capable of improving overall neural health and cognitive ability and particularly as a regimen that can sustain cognitive functions throughout one’s lifetime. Limitation of the studies Most of the BDNF related studies are on animals and correlations were made to human nervous system.

References:

• Vaynman S and Pinilla FG (2005): License to run: Exercise Impacts Functional Plasticity in the intact and Injured Central Nervous System by using Neutrophins. The American Society of Neurorehabilitation, 19 (4), 283-295.
• Mailoo VJ (2006): Psychoneuroimmunology and Occupational Therapy for Inflammatory Disorders. International Journal of Therapy and Rehabilitation, 13 (11), 503-510.
• Kischka U (2005) :The Central Nervous System. Pathophysiology: An essential text for the allied health professions , Elesevier Butterworth Heinemann, 309-319.
• Chen R, Cohen LG and Hallett M (2005): Nervous System Reorganization following injury. Pathophysiology: An essential text for the allied health professions , Elesevier Butterworth Heinemann, 325- 330.

Subhajit Sengupta MSc(Trainee), PGDDRM, BSc (OT)