In vivo profiling reveals a competent heat shock response in adult neurons: Implications for neurodegenerative disorders

TY - JOUR

T1 - In vivo profiling reveals a competent heat shock response in adult neurons

T2 - Implications for neurodegenerative disorders

AU - Carnemolla, Alisia

AU - Lazell, Hayley

AU - Moussaoui, Saliha

AU - Bates, Gillian P.

PY - 2015/7/2

Y1 - 2015/7/2

N2 - The heat shock response (HSR) is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders.

AB - The heat shock response (HSR) is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders.

UR - http://www.scopus.com/inward/record.url?scp=84940069341&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0131985

DO - 10.1371/journal.pone.0131985

M3 - Article

AN - SCOPUS:84940069341

SN - 1932-6203

VL - 10

JO - PL o S One

JF - PL o S One

IS - 7

M1 - e0131985

ER -