Neonatal propofol anesthesia modifies activity‐dependent processes and induces transient hyperlocomotor response to d‐amphetamine during adolescence in rats

Abstract

This study examined the influence of propofol anesthesia on the expression of activity-regulated molecules (BDNF and c-Fos) and synaptic plasticity markers (synaptophysin, GAP-43, drebrin) in the frontal cortex and thalamus of 7-day-old (P7) rats. Although these brain regions are the main targets of anesthetic action, they are contained in the cortico-striato-thalamo-cortical feedback loops, involved in naturally occurring and drug-induced psychoses. Therefore, functional integrity of these loops was examined in adolescent and adult rats through d-amphetamine-induced hyperactivity. Propofol treatment (25mg/kg) decreased exon-specific and total BDNF mRNA expression in the frontal cortex and thalamus, in a time-dependent manner. BDNF protein level was increased in the frontal cortex and decreased in the thalamus, which was accompanied by the change of phospho-TrkB expression. Similarly to BDNF, the expression of c-Fos was decreased in the frontal cortex while it was changed only at the protein level in the thalamus. Synaptic plasticity markers changed in a time- and region-specific manner, indicating increased synaptogenesis in the frontal cortex and synapse elimination in the thalamus in P7 rats after the propofol anesthesia exposure. These early molecular changes were followed by time-related, increased motor reaction to d-amphetamine in adolescent, but not in adult rats. Our study revealed that exposure of immature brain to propofol anesthesia during the critical phase of development provoked immediate changes in activity-dependent processes and synaptic adjustment, influencing brain capacity to integrate later developmental events and resulting in temporary altered response to acute psychotropic stimulation during adolescence.

Caffeine combined with sedative/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity

“…Notably, exposure of immature brain cells to CAF or SADs reduces mRNA and protein levels of BDNF [6,24–26], and altered BDNF expression by CAF or SADs has been implicated in neuroapoptosis [27] and long-term neurodevelopmental impairment [25,28]. In addition, CAF [29] and SADs [27,28] have been shown to downregulate activity of the pro-survival Akt pathway.…”

The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats

“…In the current study, only dorsal two‐thirds of the hippocampus was used. For immunohistochemical study, the whole brains were isolated from controls and animals 24 hour after the PAE (n = 3 per group) and subjected to fixation and cryoprotection . Animals were decapitated using a rat guillotine without anesthesia, to avoid basic results being affected.…”

Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats

“…The samples were stored at −80°C. For immunohistochemical study, the whole brains were isolated from controls and animals 24 hour after the propofol exposure (n=3 per group) and subjected to fixation and cryoprotection . Animals were decapitated using a rat guillotine without anesthesia to avoid basic results being affected.…”

“…Our protocol for Western blotting procedure has previously been published . The following primary antibodies (Santa Cruz Biotechnology) were used: anti‐D1DR (sc‐31478), anti‐DARPP‐32 (sc‐271111), anti‐DARPP‐32 (phospho‐Thr34) (pDARPP‐32; sc‐135687), anti‐ Finkel‐Biskis‐Jinkins murine osteosarcoma viral oncogene homolog‐B (FosB; sc‐7203), anti‐CaMKIIα (sc‐9035), and anti‐CaMKIIα (phospho‐Thr286) (pCaMKIIα; sc‐12886R).…”

“…Our protocol for tissue preparation has previously been published . After several washes in 0.01 M PBS, brain sections (30 μm thick) were incubated with 0.1% Triton‐X 100 (15 minutes) and 5% normal goat serum (1 hour) afterwards.…”