Disertasi

Efek Neuroprotektif N-Asetilsistein Terhadap Gangguan Memori yang Diinduksi oleh Sleep Deprivation: Penelitian Eksperimental pada Tikus Muda = Neuroprotective Effect of N-Acetylcysteine Against Memory Impairment Induced by Sleep Deprivation: An Experimental Study in Juvenile Rats.

Latar Belakang Sleep deprivation (SD) merupakan gangguan tidur dalam hal berkurangnya kuantitas maupun kualitas tidur. SD terjadi pada 20-30% anak-anak, di mana terjadi dampak buruk pada fungsi kognitif, termasuk memori. Saat ini, belum ada pengobatan standar untuk gangguan tidur ini. Dari berbagai studi pada hewan coba dan manusia, N-acetylcysteine (NAC) diketahui memiliki efek neuroprotektif. Akan tetapi, belum ada penelitian terkait efek NAC pada tikus muda yang mengalami SD. Metode 48 ekor Sprague-Dawley jantan usia 21 hari dibagi empat kelompok. Kelompok satu merupakan tikus normal tanpa SD. Kelompok dua, tiga, dan empat diinduksi SD dengan metode multiple platform yang dilakukan selama 3 hari. NAC diberikan secara intraperitoneal dengan dosis masing-masing 100 mg/kgBB atau 500 mg/kgBB pada kelompok tiga dan empat selama 5 hari (dimulai sejak 2 hari sebelum perlakuan SD). Fungsi kognitif dinilai dengan y-maze dan NOR. Dilakukan pemeriksaan kadar kortisol dan IL-1β pada darah. Pada hipokampus, dilakukan pemeriksaan aktivitas enzim AChE, kadar ACh, BDNF, CREB, p-CREB, dan penilaian densitas neuron. Ekspresi mRNA dari IL-1β, TNF-α, dan NLRP3 dari jaringan PFC juga dinilai. Hasil Pada kelompok SD tanpa NAC, terjadi penurunan alternasi spontan dan rasio diskriminasi secara signifikan (p < 0.05) dibandingkan kelompok normal. Hal tersebut diikuti pula dengan penurunan kadar BDNF yang bermakna, serta tendensi peningkatan aktivitas AChE dan penurunan ACh dibandingkan kelompok normal. Kadar kortisol dan ekspresi mRNA TNF-α pada kelompok tersebut juga meningkat secara signifikan dibanding kelompok normal. Pemberian NAC terutama pada dosis 500 mg/kgBB memberikan hasil yang bermakna pada peningkatan alternasi spontan, rasio diskriminasi, dan kadar BDNF, serta penurunan kadar kortisol, aktivitas enzim AChE, dan ekspresi mRNA TNF-α. Kesimpulan NAC dapat mencegah defisit memori yang diinduksi SD dengan menurunkan ekspresi mRNA TNF-α, aktivitas AChE, kadar kortisol, dan meningkatkan kadar BDNF.
Kata Kunci: TNF-α, BDNF, aktivitas AChE, kadar kortisol


Introduction Sleep deprivation (SD) is a sleep disorder in terms of reduced quantity or quality of sleep. SD occurs in 20-30% of children, with negative impacts on cognitive function, including memory. Currently, there is no standard treatment for this condition. From various studies on experimental animals and humans, Nacetylcysteine (NAC) is known to have neuroprotective effects. However, no research related to the effects of NAC in juvenile rats with SD. Method 48 male Sprague-Dawley rats aged 21 days were divided into four groups. Group one was normal rats without SD. Groups two, three, and four were induced with SD using the multiple-platform method for 3 days. NAC was administered intraperitoneally at a dose of 100 mg/kgBW or 500 mg/kgBW in groups three and four for 5 days (starting 2 days before SD treatment). Cognitive function was assessed using y-maze and NOR. Blood cortisol and IL-1β levels were examined. In the hippocampus, AChE enzyme activity, ACh, BDNF, CREB, p-CREB levels, and neuron density were measured. mRNA expression of IL-1β, TNF-α, and NLRP3 from PFC tissue was also assessed. Results In the SD group without NAC, there was a significant decrease in spontaneous alternation and discrimination ratio (p < 0.05) compared to the normal group. This was also followed by a significant decrease in BDNF levels and a tendency to increase AChE activity and decrease ACh compared to the normal group. Cortisol levels and TNF-α mRNA expression in this group also increased significantly compared to the normal group. Administration of NAC, especially at a dose of 500 mg/kg BW, gave significant results in increasing spontaneous alternation, discrimination ratio, and BDNF levels and decreasing cortisol levels, AChE enzyme activity, and TNF-α mRNA expression. Conclusion NAC prevents SD-induced memory deficits by decreasing TNF-α mRNA expression, AChE activity, and cortisol levels, and increasing BDNF levels.
Keywords: TNF-α, BDNF, AChE activity, cortisol level