Immunohistochemical analysis of sympathetic involvement in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disorder caused by degeneration of motor neurons in the cerebral cortex, brainstem and spinal cord. Several clinical reports indicated sympathetic and parasympathetic dysfunction in ALS patients. In addition, we have recently reported elevated heart rate and blood pressure in transgenic (TG) mice carrying the SOD1 mutant form of the human SOD1 transgene (SOD1-G93A) even prior to the appearance of motor symptoms. In order to further elucidate the mechanisms underlying autonomic impairment in ALS we performed an immunohistochemical study of the intermediolateral nucleus (IML) column neurons (T2 − L2), superior cervical ganglia (SCG) and adrenal glands (AG) in TG and littermate wild-type (WT) mice at the age of 75 − 80 days. IML column neurons sections were stained with antibodies against choline acetyltransferase (ChAT), SOD1, ubiquitin and SMI31. SCG and AG sections were stained with antibodies against ChAT and tyrosine hydroxylase (TH). ChAT is predominantly located at preganglionic nerve terminals that innervate the AG, while TH is located in sympathetic neurons. Results showed that ChAT, SOD1 and ubiquitin expressions in IML column were significantly lower in the SOD1-G93A group compared to WT (p < 0.0001, p = 0.0042 and p < 0.0001, respectively). SMI31 measurements did not reveal any statistical differences between the two groups (p = 0.6187). TH expression in AG revealed a 24% decrease in the SOD1-G93A group compared to WT (p < 0.0001), while ChAT expression in the SCG was reduced by 28% (p < 0.0001). No significant differences were found for TH in SCG or for ChAT in AG. In conclusion, these results are consistent with preganglionic sympathetic denervation as a potential contributor to the abnormal sympathetic regulation in ALS.

Key words::

• Amyotrophic lateral sclerosis
• SOD1-G93A
• superior cervical ganglion
• adrenal gland
• tyrosine hydroxylase
• choline acetyltransferase
• autonomic function
• transgenic animals

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.