Restoration of brain protein synthesis in mature and aged rats by a DA agonist, piribedil

Abstract

Summary— Brain ageing affects numerous cerebral metabolic pathways such as cerebral glucose consumption or protein synthesis rate. The pharmacological effect of a mixed D1‐D2 dopaminergic agonist, piribedil, on this last metabolism is reported. Cerebral Protein Synthesis Rate (CPSR) was measured by the [35S]L‐methionine autoradiographic procedure in 38 main brain regions of 11 and 26‐month‐old Wistar rats after a 2‐month treatment per os at 9 and 30 mg/kg/day with piribedil. Mean decrease of CPSR was −21% during the 15‐month ageing we followed, with important local variations. Mean CPSR increased with the two treatments, +25% in mature and +35% in aged rats. Treatments restored CPSR of aged rats to the exact mature subjects levels in quite all the brain regions. No dose‐effect or asymetrical modification was statistically revealed for the two treatments. Metabolic increases involved particularly central brain gray structures, especially some DA‐targeted brain nuclei concerned with behaviour and learning. This effect argued for a general metabotrophic effect of D1‐D2 dopamine stimulation of the brain. The original pattern of local ageing of brain protein synthesis in rat was also incidentally reported. This was the first direct report of a wide and effective metabolic activation of CPSR in the brain during ageing by a curative dopaminergic agonist treatment.

Target Identification for CNS Diseases by Transcriptional Profiling

“…Aging may be a factor responsible for cell-type-specific downregulation of many genes (Lu et al , 2004), with downregulation of DA receptor gene expression contributing to deficits in learning and memory, anxiety, and depressive-like syndromes during aging. It is of interest that the D2/D3 agonist piribedil, which increases cognitive skill learning in aged adults (Peretti et al , 2004), restores the 21% decrease in brain protein synthesis rates in aged rats as compared with those of middle-aged rats (Bustany et al , 1995). …”

A Light Microscopic Radioautographic Study on Protein Synthesis in Pulmonary Cells of Aging Mice.

“…It is one of the biochemical processes that has been shown to change with increasing age in various tissues and organs, such as the muscle [19], heart [37], spleen [37], small and large intestines [15], liver [18,[20][21][22][23], pancreas [31][32][33][34], kidney [13,37], testis [8][9][10][11], uterus [44], retina [42] and brain [5,24].…”