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Prolyl endopeptidase mRNA expression in the central nervous system during rat development
N Agirregoitia1, P Bizet, E Agirregoitia
1INSERM U413/U982, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France. naiara.aguirregoitia@ehu.es
Insights
Prolyl endopeptidase (PEP) mRNA is present early in rat brain development, particularly in neuroepithelial and differentiating cells. PEP expression is highest during perinatal stages, suggesting roles in neurodevelopment beyond its known brain functions.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Prolyl endopeptidase (PEP) is a serine protease implicated in learning, memory, psychological disorders, and neurodegenerative diseases.
- PEP substrates are known to play roles in brain development.
- The precise developmental functions of PEP remain largely unexplored.
Purpose of the Study:
- To investigate the spatiotemporal expression of Prolyl endopeptidase (PEP) mRNA in the developing rat brain and spinal cord.
- To determine the correlation between PEP mRNA expression patterns and key neurodevelopmental processes.
Main Methods:
- In situ hybridization was used to visualize PEP mRNA distribution in embryonic and postnatal rat tissues.
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was employed to quantify PEP mRNA levels in various brain regions and the spinal cord across different developmental stages.
Main Results:
- PEP mRNA expression was detected early in development (embryonic day 15) in various germinative and differentiating areas of the brain, including the neocortex, hippocampus, and cerebellum.
- PEP mRNA levels were highest during perinatal stages, coinciding with periods of neuronal migration and differentiation.
- PEP mRNA expression significantly decreased from postnatal stages to adulthood, reaching minimal levels in adult rats.
Conclusions:
- The study reveals a distinct expression pattern of PEP mRNA during rat neurodevelopment, with peak expression during critical periods of neuronal formation and maturation.
- These findings suggest that PEP plays a significant role in neurodevelopmental processes, in addition to its previously recognized functions in adult brain physiology.
- Further research is warranted to elucidate the specific molecular mechanisms through which PEP influences brain development.
Abstract:
Prolyl endopeptidase (PEP) is a serine protease that cleaves small peptides at the carboxyl side of L-proline. PEP has been reported to have important functions in the brain being implicated in learning and memory processes, psychological disorders and neurodegenerative diseases. Several PEP substrates have been shown to play a role during brain development and this observation led us to investigate the expression of PEP mRNA in the rat brain and spinal cord, from embryo to adult stages. In situ hybridization revealed that PEP mRNA is expressed early, from embryonic day 15, notably in germinative areas including the neocortical, hippocampal, pallidal, thalamic, anterior hypothalamic, tectal, cerebellar, pontine and medullary neuroepithelia. PEP mRNA was also found in the differentiating fields of the olfactory bulb, the orbital and cingulate cortex, the hippocampal formation, the cortical plate and the subventricular zone of the cortex. Quantitative RT-PCR analysis in various brain areas and the spinal cord showed that PEP mRNA levels are more abundant during the perinatal stages, coinciding with a period of neuronal migration and differentiation. From then on, PEP mRNA expression decreased, reaching its lowest levels at adulthood. Overall, the present data support the possibility that PEP exerts specific functions related to neurodevelopment besides those proposed to date.
