Fizyolojik yaşlanma sürecinde prefrontal korteks biyojen aminler ve MAO inhibitörlerinin etkileşimi
Küçük Resim Yok
Tarih
1999
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Yaşlanma süreci, insan populasyonun artan ortalama yaşam süresine bağlı olarak, yaşa bağlı mental ve motor fonksiyonlarda görülen yetersizlikler ile yaşla birlikte görülme sıklığı artan nörodejeneratif hastalıkların sayısının hızla artması nedeniyle önem kazanmıştır. Fizyolojik yaşlanma ve bazı patolojilerde görülen bu fonksiyonal bozukluklarda dopaminerjik, noradrenerjik ve serotonerjik nöronlar arasındaki bütünlüğün bozulması anahtar rol oynamaktadır. Yaşlı kişilerde izlenen mental ve motor disfonksiyonların temelinde biyojenik aminler önemli rol oynamaktadır. Monoamin oksidaz (MAO), bu biyolojik aktif aminlerin metabolizmasında anahtar rol oynayan bir enzimdir. Enzimin aktivitesi yaşlanma ve diğer nörodejeneratif hastalıklarda geniş varyasyonlar gösteren değişiklikler sergiler. Bu nedenle son yıllarda, Alzheimer ve Parkinson'lu hastalar ile depresyon izlenen yaşlı populasyonda tedavi amacıyla MAO enzim inhibitörleri yaygın olarak kullanılmaktadır. Çalışmamızda öncelikle, sıçan prefrontal korteks dokusunda fizyolojik yaşlanma sürecinde adrenalin (A), noradrenalin (NA), serotonin (5-HT), dopamin (DA) ve metabolitleri normetanefrin (NMN), 5-hidroksi indol asetik asid (5-HİAA), homovanilik asid (HVA), dihidroksifenil asetik asid (DOPAC) düzeyleri ile MAO aktivitesinde oluşan değişiklikler incelenmiştir. İkinci aşamada ise yaşlanma sürecinde MAO inhibitörlerinin kronik kullanımının biyojen aminler ve metabolitleri üzerine etkileri araştırılmıştır. İlk olarak genç (2-3 aylık, n=15) ve yaşlanan (16-18 aylık, n=15) sıçan gruplarında prefrontal korteks doku MAO aktivitesi ile biyojen aminler ve metabolitleri ölçülmüştür. İkinci aşamada, genç (2-3 aylık, n=10) ve yaşlanan (16-18 aylık, n=10) sıçanlara kronik dozda (0.25 mg/kg/gün, 14 gün, I.P) MA0-B inhibitörü olan deprenil uygulanmıştır. Yaşlanan gruplarda prefrontal korteks dokusunda genç grupla karşılaştırıldığında artmış MAO enzim aktivitesi saptanmıştır (p=0.05). Yaşlanan grupta biyojen aminlerden noradrenalin ve dopamin düzeyleri (sırasıyla p=0.03,p=0.009); metabolitlerden normetanefrin, homovanilik asid ve dihidroksifenil asetik asid düzeylerinde anlamlı yükseklik saptanmıştır (sırasıyla p=0.006, p=0.001, p=0.05) .Deprenil uygulaması ile genç ve yaşlanan gruplarda enzim inhibisyonu sağlanmıştır (sırasıyla %65, %76). Enzim aktivitesindeki inhibisyona rağmen plasebo ve deprenil uygulanan gruplar arasında biyojen amin ve metabolitleri açısından anlamlı fark elde edilmemiştir.
The process of aging is becoming increasingly important as the average longevity of the population increases and the number of people with both age-associated impairment and neurodegenerative diseases of old age rises sharply. The disturbed integrity of dopaminergic, noradrenergic and serotonergic neurons is considered to be the key in the impairments seen during aging and certain diseases. Underlying of the mental and motor changes observed in the elderly population, biogenic amines seem to play an important role. Monoamine oxidase(MAO) is an enzyme responsible for the inactivation of these biologically important active amines. it is one of the most investigated enzyme presumably because of its importance in biological psychiatry. The activity of MAO displays great variances in different organs during the process of aging and in the physiopathology of certain neurodegenerative diseases. Thus in the recent years, MAO inhibition is a widely used therapeutic strategy in the treatment of Alzheimer's disease, Parkinson's disease and depression seen in the elderly. The aim of our study was to determine the changes in biogenic amines. adrenalin (A), noradrenalin (NA): serotonin (5-HT), dopamine (DA), as well as in their metabolites, normetanephrine (NMN), homovanillic acid (HVA), dihydroxyphenyl acetic acid (DOPAC), 5-hydroxyindol acetic acid (5-HİAA) occurring concurrently with the changes in MAO activity of the prefrontal cortex of aging rats. We aimed to observe the effects of MAO inhibitors on altered levels of biogenic amines and their metabolites. in the first part of this study MAO activity and the levels of biogenic amines and their metabolites were measured in the prefrontal corticies of young (2-3 months old, n=15) and aging (16-18 months old, n=15) rats. in the second step, after chronic administration of deprenyl, MAO-B inhibitor, (0.25 mg/kg/day, 14 days, I.P) the above mentioned parameters were measured in the prefrontal corticies of young (2-3 months old. n = 10) and aging (16-18 months, n=10) rats. The results showed that MAO activities in prefrontal cortex were significantly higher in the aging groups (p=0.05). As for the biogenic amines elevated levels of noradrenaline and dopamine (respectively p=0.03,p=0.009); for the metabolites elevated levels of normetanephrine, homovanillic acid and dihydroxyphenyl acetic acid were found in the aging groups (respectively p=0.006, p=0.001, p=0.05). Administration of MAO inhibitor resulted in no difference in the levels of biogenic amines between placebo and deprenyl groups in neither young nor aging groups. However MAO activities were significantly decreased (respectively %65, %76).
The process of aging is becoming increasingly important as the average longevity of the population increases and the number of people with both age-associated impairment and neurodegenerative diseases of old age rises sharply. The disturbed integrity of dopaminergic, noradrenergic and serotonergic neurons is considered to be the key in the impairments seen during aging and certain diseases. Underlying of the mental and motor changes observed in the elderly population, biogenic amines seem to play an important role. Monoamine oxidase(MAO) is an enzyme responsible for the inactivation of these biologically important active amines. it is one of the most investigated enzyme presumably because of its importance in biological psychiatry. The activity of MAO displays great variances in different organs during the process of aging and in the physiopathology of certain neurodegenerative diseases. Thus in the recent years, MAO inhibition is a widely used therapeutic strategy in the treatment of Alzheimer's disease, Parkinson's disease and depression seen in the elderly. The aim of our study was to determine the changes in biogenic amines. adrenalin (A), noradrenalin (NA): serotonin (5-HT), dopamine (DA), as well as in their metabolites, normetanephrine (NMN), homovanillic acid (HVA), dihydroxyphenyl acetic acid (DOPAC), 5-hydroxyindol acetic acid (5-HİAA) occurring concurrently with the changes in MAO activity of the prefrontal cortex of aging rats. We aimed to observe the effects of MAO inhibitors on altered levels of biogenic amines and their metabolites. in the first part of this study MAO activity and the levels of biogenic amines and their metabolites were measured in the prefrontal corticies of young (2-3 months old, n=15) and aging (16-18 months old, n=15) rats. in the second step, after chronic administration of deprenyl, MAO-B inhibitor, (0.25 mg/kg/day, 14 days, I.P) the above mentioned parameters were measured in the prefrontal corticies of young (2-3 months old. n = 10) and aging (16-18 months, n=10) rats. The results showed that MAO activities in prefrontal cortex were significantly higher in the aging groups (p=0.05). As for the biogenic amines elevated levels of noradrenaline and dopamine (respectively p=0.03,p=0.009); for the metabolites elevated levels of normetanephrine, homovanillic acid and dihydroxyphenyl acetic acid were found in the aging groups (respectively p=0.006, p=0.001, p=0.05). Administration of MAO inhibitor resulted in no difference in the levels of biogenic amines between placebo and deprenyl groups in neither young nor aging groups. However MAO activities were significantly decreased (respectively %65, %76).
Açıklama
Anahtar Kelimeler
Geriatri ve Gerontoloji
Kaynak
Geriatri
WoS Q Değeri
Scopus Q Değeri
Cilt
2
Sayı
4
