隨著年紀變大,，我們的記性開始變差，經(jīng)常忘了車鑰匙放哪里,，或者想不起那個經(jīng)常見面的人的名字?，F(xiàn)在一項新研究找到了這種所謂工作記憶“認知缺失”的原因,，并認為這種情況可以逆轉(zhuǎn)。
美國耶魯大學(xué)科研人員發(fā)現(xiàn),，相比年輕人，中老年人大腦的神經(jīng)網(wǎng)絡(luò)連接更為脆弱,，活動也不那么頻繁。正如他們在《自然》周刊上所指出的那樣,，對動物的實驗證明，可以用當前治療高血壓的一種藥物來扭轉(zhuǎn)這種認知缺失,。
隨著年紀變大,，人變得越來越容易忘事或者難以集中注意力,，一些認知功能也難以完成,。雖然很長時間以來大家都認為這種缺失與年齡有關(guān),，但至今還不知道造成這種認知缺失的生物學(xué)原因,。
耶魯大學(xué)神經(jīng)科學(xué)研究人員對處于青年、中年和老年三個不同年齡段的猴子進行研究,，分析它們前額葉皮層（大腦負責(zé)認知功能和解決問題的區(qū)域）神經(jīng)細胞的活動如何隨著衰老而變化,。
這些猴子被要求進行一些需要使用工作記憶的活動,，例如回想目標物放置地、組織表演或同時進行多項活動等,。研究人員發(fā)現(xiàn)，青年猴子前額葉皮層的神經(jīng)連接能夠在實驗活動中保持高頻率的“放電”,，而年老猴子神經(jīng)細胞放電程度更弱且時間更短,。
然而當科研人員使用一種化學(xué)成分封鎖神經(jīng)信號重復(fù)這些實驗時，卻使這種神經(jīng)細胞損壞得到修復(fù),，年老猴子達到與青年猴子相似的活動水平,。
科研人員認為，衰老會導(dǎo)致一種被稱為cAM P的分子過度積累,，它可能導(dǎo)致神經(jīng)信號變?nèi)?。使用某些化學(xué)成分封鎖或者禁止這類分子的活動就可以逆轉(zhuǎn)神經(jīng)細胞的信號連接方式,，改善它們的功能。
因年紀變大而產(chǎn)生的認知缺失會給生活帶來嚴重影響,，妨礙我們工作或獨立生活能力,。研究人員認為，現(xiàn)有藥物能夠改善神經(jīng)聯(lián)系功能,，其中一種用于治療高血壓的藥物能夠禁止cAM P分子的活動，修復(fù)工作記憶,，但任何藥物都有待進一步的臨床驗證方可使用。(生物谷 Bioon.com)
doi:10.1016/j.cell.2005.08.020
PMC:
PMID:
Neuronal basis of age-related working memory decline
Min Wang; Nao J. Gamo; Yang Yang; Lu E. Jin; Xiao-Jing Wang; Mark Laubach; James A. Mazer; Daeyeol Lee; Amy F. T. Arnsten
Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction1, 2, 3, 4. The PFC guides behaviour and thought using working memory5, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation6. This fragile process is highly dependent on the neurochemical environment7. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels8, 9. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.
