The serotoninergic bulbospinal system and brainstem-spinal cord content of serotonin-, TRH-, and substance P-like immunoreactivity in the aged rat with special reference to the spinal cord motor nucleus.
The 5-hydroxytryptamine (5HT) containing bulbospinal pathway was studied with immunohistochemical (IF) and chemical techniques in 2-3 and 30 months old male Sprague-Dawley rats. The coexisting neuropeptides substance P (SP), thyrotropin-releasing hormone (TRH) and galanin were also analysed. Furthermore, the expression of mRNA encoding aromatic L-amino acid decarboxylase (AADC), prepro-TRH, and preprotachykinin (prepro-SP) was analysed with in situ hybridization (ISH) in the midline raphé nuclei inthe lower brainstem. The results showed a decreased number of axonal 5HT fibers with a normal morphology in the ventral horn of the aged rat lumbosacral spinal cord, and several 5HT immunoreactive (IR) fibers with an aberrant morphology, suggestive of axonal degeneration, were intermingled. This was evident in both the dorsal and ventral horn of the spinal cord. The 5HT-IR fibers with an aberrant morphology usually also contained TRH-and/or SP- and/or galanin-like immunoreactivity (LI) in the ventral horn. These signs of degeneration were clearly less evident in the thoracic and cervical spinal cord segments. Moreover, these changes varied between aged litter-mates. This was in agreement with behavioural signs of motor disturbances, present in about 40% of the aged rats and which in all cases were confined to the hindlimbs. Chemical analyses disclosed significantly lower levels of TRH-LI and, in particular, SP-LI in both the ventral and dorsal quandrants of the spinal cord in the aged rat compared to young adults. The differences were largest in the lumbar regions of the spinal cord. Corresponding analysis of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in the same tissue specimens revealed largely unaltered levels of 5HT and a slight increase in 5HIAA, indicating the possibility of an increased 5HT turnover in the aged rat spinal cord. Neurons in nucleus raphé obscurus and nucleus raphé pallidus were immunoreactive to 5HT, and after pretreatment with colchicine to TRH-, SP-, and galanin-LI as well. There was no obvious difference in number of labeled cells, or labeling intensity, between colchicine-treated young adult and aged rats, although, in the corresponding region of medulla oblongata, chemical analysis disclosed significantly lower levels of 5HT, TRH, and, in particular, SP in untreated aged rats. In contrast, in situ hybridization analysis revealed increased mRNA levels encoding prepro-TRH and prepro-SP in old rats, while mRNA content encoding AADC mRNA was similar in young adult and aged rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Johnson
H
H
Department of Anatomy, Karolinska Institutet, Stockholm, Sweden.
Ulfhake
B
B
Dagerlind
A
A
Bennett
G W
GW
Fone
K C
KC
Hökfelt
T
T
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D001933:Brain Stem / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D019004:Galanin; D015870:Gene Expression; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008959:Models, Neurological; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009410:Nerve Degeneration; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011903:Raphe Nuclei / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013373:Substance P / Q000032:analysis / Q000378:metabolism*; D015320:Tachykinins / Q000096:biosynthesis; D013973:Thyrotropin-Releasing Hormone / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*
D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; C063596:prepro-thyrotropin-releasing hormone; D012701:Serotonin; D013373:Substance P; D006897:Hydroxyindoleacetic Acid; D013973:Thyrotropin-Releasing Hormone; D019004:Galanin; D001142:Aromatic-L-Amino-Acid Decarboxylases