Regeneration: Role of Nerotrophins and Nanotubes Malathi Srivatsan, Ph.D. Associate Professor, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72401

Our Constantly Changing NS & Neuronal Plasticity  Neurons being post- mitotic, have to be viable for the entire life span and hence have to constantly adapt to the changing environment.  Successful Adaptation : synaptic plasticity, regeneration.  Maladaptation or failure to adapt: neuron death, degeneration

Finding Cures for Neurodegeneration is a formidable and crucial Challenge While regeneration is possible in PNS, hardly any Regeneration happens at CNS! Result = neuron loss, functional impairment for rest of the life Each year 10,000 new spinal cord injury occurs in USA 4.5 million patients currently suffer from AD in USA In the United States, it is estimated that 60,000 new cases are diagnosed each year, joining the 1.5 million Americans who currently have Parkinson's disease.

Strategies to Promote Regeneration  Infusion of Trophic factors  Guiding growing axons (neurites) to appropriate targets  Strengthen axons and synapses by stimulation  Stem cell therapy Nanomaterials can contribute significantly to all of these measures !

Basis for AChE’s possible diverse functions (new?): AChE’s appearance even before the evolution of a distinct nervous system AChE’s widespread presence in non-cholinergic sites The multiple isoforms that are expressed in a tissue- specific manner It’s sequence homology with thyroglobin and identity with cell adhesive molecules (glutactin, neurotactin)

DRG neurons of rat express AChE DRG neurons are not cholinergic There are no synapses in DRG DRG neurons can be maintained as neuron enriched cultures DRG Neurons of Rat is a Good Model to Study AChE Effects in vitro & in vivo

AChE promotes growth of multiple neurites in DRG neurons via a non-catalytic mechanism

AChE promotes neurite growth of DRG neurons in time and dose-dependent manner 24hrs 48hrs

AChE enhances survival of DRG neurons in culture

Acetylcholinesterase binds to neurons as well as growing neurites

Gene Expression Altered by AChE

Nano neuro interaction CNTs can be a good, growth promoting substratum for sensory neurons Functionalized CNTsNon-functionalized

Nanotubes can be coupled with Growth factor for Neurons Nanotube coupled with nerve growth factor Growing lamellipodium of neurite A

MNTs are Neuroprotective and need to be explored for Enhancing Neuron Survival  MNTs are biocompatible as revealed by reduced LDH release  MNT bound NGF was available to PC 12 Cells  MNTs themselves promote survival and differentiation

Maghemite nanorings (MNR) are neuron friendly 1314 In ~ 9.7 Gauss magnetic field 56 No magnetic field

Our Team & Collaborators Funding from: NIH/INBRE NSF NIH/NIDA AR State Funds